ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2015
Phosphodiesterase-4 (PDE4) molecular pharmacology and Alzheimer's disease.
Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02835716 (Pre-Clinical Alzheimer's), which is not on this map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pre-Clinical Alzheimer's (ALZ) Diagnosis (PCD) = Optimum Outcomes (OO)
Who cites it
57 citing papers in PubMed, 117 citations in OpenAlex.
- A Narrative Review: Do Systemic Drugs Used in the Treatment of Psoriatic Disease Affect Alzheimer's Disease?Dermatology and therapy · 2026Review
- Variecolactone, a Natural PDE4 Inhibitor from Marine-DerivedBiomolecules · 2026Article
- Dual PDE4/10A inhibition restores CREB1 function and enhances neuronal resilience in models of alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Correlation of autophagy and Alzheimer's disease with special emphasis on the role of phosphodiesterase-4.3 Biotech · 2025Review
- Apremilast reduces co-occurring alcohol drinking and mechanical allodynia and regulates central amygdala GABAergic transmission.JCI insight · 2025Article
- Pterostilbene: A natural neuroprotective stilbene with anti-Alzheimer's disease properties.Journal of pharmaceutical analysis · 2025Review
- Inhibition of PDE4B ameliorates cognitive defects in the model of alcoholic dementia in 3xTg-AD mice via PDE4B/cAMP/PKA signaling.The international journal of neuropsychopharmacology · 2025Article
- Molecular Properties of Phosphodiesterase 4 and Its Inhibition by Roflumilast and Cilomilast.Molecules (Basel, Switzerland) · 2025Review
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Review
- Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice.Cells · 2024Article
- Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma.Scientific reports · 2024Article
- Article
- Anti-Neurodegenerating Activity: Structure-Activity Relationship Analysis of Flavonoids.Molecules (Basel, Switzerland) · 2023Article
- Drug Discovery and Development Targeting Dementia.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
- Pharmacological modulation of phosphodiesterase-7 as a novel strategy for neurodegenerative disorders.Inflammopharmacology · 2022Review
- The relationships between neuroglial and neuronal changes in Alzheimer's disease, and the related controversies II:Journal of central nervous system disease · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Between 20% and 25% of patients diagnosed with Alzheimer's disease (AD) do not have amyloid burden as assessed by positron emission tomography imaging. Thus, there is a need for nonamyloid-directed therapies for AD, especially for those patients with non-amyloid AD. The family of phosphodiesterase-4 (PDE4) enzymes are underexploited therapeutic targets for central nervous system indications. While the PDE4A, B, and D subtypes are expressed in brain, the strict amino acid sequence conservation of the active site across the four subtypes of PDE4 has made it difficult to discover subtype inhibitors. The recent elucidation of the structure of the PDE4 N- and C-terminal regulatory domains now makes it possible to design subtype-selective, negative allosteric modulators (PDE4-NAMs). These act through closing the N-terminal UCR2 or C-terminal CR3 regulatory domains, and thereby inhibit the enzyme by blocking access of cyclic adenosine monophosphate (cAMP) to the active site. PDE4B-NAMs have the potential to reduce neuroinflammation by dampening microglia cytokine production triggered by brain amyloid, while PDE4D-NAMs have potent cognitive benefit by augmenting signaling through the cAMP/protein kinase A/cAMP response element-binding protein (CREB) pathway for memory consolidation. The importance of PDE4D for human cognition is underscored by the recent discovery of PDE4D mutations in acrodysostosis (ACRDY2: MIM 600129), an ultra rare disorder associated with intellectual disability. Thus, the family of PDE4 enzymes provides rich opportunities for the development of mechanistically novel drugs to treat neuroinflammation or the cognitive deficits in AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.